What is alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency (AATD) is an inherited condition that causes low levels of, or no, alpha-1 antitrypsin (AAT) in the blood. AATD occurs in approximately 1 in 2,500 individuals. This condition is found in all ethnic groups; however, it occurs most often in whites of European ancestry.

Alpha-1 antitrypsin (AAT) is a protein that is made in the liver. The liver releases this protein into the bloodstream. AAT protects the lungs so they can work normally. Without enough AAT, the lungs can be damaged, and this damage may make breathing difficult.

Everyone has two copies of the gene for AAT and receives one copy of the gene from each parent. Most people have two normal copies of the alpha-1 antitrypsin gene. Individuals with AATD have one normal copy and one damaged copy, or they have two damaged copies. Most individuals who have one normal gene can produce enough alpha-1 antitrypsin to live healthy lives, especially if they do not smoke.

People who have two damaged copies of the gene are not able to produce enough alpha- 1 antitrypsin, which leads them to have more severe symptoms.

What are the signs and symptoms of AATD?

Alpha-1 antitrypsin deficiency (AATD) can present as lung disease in adults and can be associated with liver disease in a small portion of affected children. In affected adults, the first symptoms of AATD are shortness of breath with mild activity, reduced ability to exercise, and wheezing. These symptoms usually appear between the ages of 20 and 40.

Other signs and symptoms can include:

• repeated respiratory infections
• fatigue
• rapid heartbeat upon standing
• vision problems
• unintentional weight loss.

How would you expect your physician to diagnose AATD?

Alpha-1 antitrypsin deficiency (AATD) is diagnosed through testing of a blood sample, when a person is suspected of having AATD. For example, AATD may be suspected when a physical examination reveals a barrel-shaped chest, or, when listening to the chest with a stethoscope, wheezing, crackles or decreased breath sounds are heard.

Testing for AATD, using a blood sample from the individual, is simple, quick and highly accurate.

Three types of tests are usually done on the blood sample:

• Alpha-1 genotyping, which examines a person’s genes and determines their genotype.
• Alpha-1 antitrypsin PI type of phenotype test, which determines the type of AAT protein that a person has.
• Alpha-1 antitrypsin level test, which determines the amount of AAT in a person’s blood.

Individuals who have symptoms that suggest AATD or who have a family history of AATD should consider being tested.

How to manage AATD?

Treatment of alpha-1 antitrypsin deficiency (AATD) is based on a person’s symptoms. There is currently no cure. The major goal of AATD management is preventing or slowing the progression of lung disease.

Treatments include bronchodilators and prompt treatment with antibiotics for upper respiratory tract infections. Lung transplantation may be an option for those who develop end-stage lung disease. Quitting smoking, if a person with AATD smokes, is essential.

Replacement (augmentation) therapy with the missing AAT protein is available, although it is used only under special circumstances. It is not known how effective this is once disease has developed or which people would benefit most.